cytochrome-c-t and Lymphoma--T-Cell--Cutaneous

Constitutive active NF-kappaB have been shown to protect cutaneous T cell lymphoma (CTCL) cells from apoptosis. In the present study, we have studied the cytotoxic potential of nitric oxide generating compound, sodium nitroprusside (SNP) on CTCL cell line, HuT-78. Treatment of cells with SNP resulted in decrease in mitochondrial membrane potential, cytochrome c release, activation of caspase-3 and poly (ADP ribose) polymerase cleavage. SNP treatment inhibited activation of NF-kappaB in a concentration dependent manner. SNP increased the expression of IkappaBalpha without affecting the phosphorylation of IkappaBalpha. Downregulation of NF-kappaB by SNP decreased p65 nuclear translocation as evident by confocal fluorescence microscopy. Further it was found that SNP treatment caused downregulation of Bcl-2 family member (Bcl-xl) in HuT-78 cells. Thus, we have provided evidence that SNP induces apoptosis in CTCL cell line, HuT-78 by downregulating constitutive NF-kappaB and thereby Bcl-xl expression.

Topics: Apoptosis; Caspase 3; Cell Line, Tumor; Cell Survival; Cytochromes c; Dose-Response Relationship, Drug; Enzyme Activation; Gene Expression Regulation, Neoplastic; Humans; I-kappa B Proteins; Lymphoma, T-Cell, Cutaneous; Membrane Potential, Mitochondrial; NF-kappa B; NF-KappaB Inhibitor alpha; Nitric Oxide; Nitric Oxide Donors; Nitrites; Nitroprusside; Transcription Factor RelA